The present invention relates to administration of medical powders into the respiratory tract by releasing powder to be inhaled and more particularly to a dry powder inhaler dispensing a pre-metered dose of medical powder during a prolonged inhalation process.
The administration of drugs is carried out in a number of different ways in the medical service today. Within health care more and more is focussed on the possibility to dose and distribute powder directly to the lungs of a user by means of an inhaler to obtain effective, quick, and user friendly administration of such substances.
A dry powder inhaler of today, (DPI), represents a device intended for administration of powder into the deep or upper lung airways by oral inhalation. With deep lung should be understood the peripheral lung and alveoli, where direct transport of active substance to the blood can take place. Particle sizes, to reach into the deep lung, should be in a range 0.5-3 xcexcm and for a local lung delivery in the range 3-5 xcexcm. A larger grain size will easily stick in the mouth and throat, and a smaller grain size may accompany the expiration air out again.
Administration of medical powders into the respiratory tract is a very attractive way for administration of many substances both for local treatments and for systemic treatments. To administer electrostatically dosed drugs by a dry powder inhaler (DPI) through the lung some very important technical basic factors must be met by the system.
A correct dose with a high uniformity of dose is desired from the inhaler. For electrostatically dosed medical substances the relative standard deviation between doses (RSD) should preferably be not more than 5%.
However, powder having a small grain size will demonstrate a strong tendency to agglomerate, i.e. to clod into larger grains. In the inhalers being used at the moment a large portion of the powder is agglomerated when it is dosed and much powder therefore will stick to the upper respiratory tracts. Technologies for de-agglomeration include advanced mechanical and aerodynamic systems and combinations between electrical and mechanical filling systems that can be seen in for instance U.S. Pat. No. 5,775,320, U.S. Pat. No. 5,785,049 and U.S. Pat. No. 5,740,794.
It is also common to utilize carriers having a larger grain size onto which the fine power is distributed. Upon inspiration the large size grains will stick in the oral cavity while the small grains will be let free and proceed to the lung.
One of the problems upon inhalation of a medical powder is that a relatively large portion of the dose will also stick in the inhaler device. To be able to include all powder and disassemble agglomerates a high air velocity is needed. From a dose given by the inhaler the respiratory dose (grain size less than 5 xcexcm) may often be only 20%.
For achieving a high respiratory dose often a socalled spacer is used to have the small grains evenly distributed in a container from which the inhalation can take place. In principle a dosing device or an inhaler is connected to a container having a relatively large volume and into this container a powder or an aerosol is injected which partly is distributed in the air space and partly sticks to the walls. Upon inhalation from the spacer the fine powder floating free in the air will effectively reach the alveoli. This method in principle has two drawbacks, firstly difficulties to control the amount of medicine emitted to the lung as uncontrolled amount of powder sticks to the walls of the spacer and secondly difficulties in handling the relatively space demanding apparatus to be desired when it comes to dosage conformity and lung deposition effectiveness of the medical substance.
To meet some of these demands an electrostatic dosing of the powder onto a technical means for example a cassette can by done. An electrostatic dosing onto a device member or cassette was described in our Swedish Patent No. 9802648-7 (SE512 433) and the quality can be improved by utilizing the possibility to classify coarse particles larger than 5 xcexcm to leave those out and dose only fine particles (less than 5 xcexcm) onto the device member or cassette as described in our Swedish Patent No. 9802649-5 (SE512 386).
However, still there is a demand for a device sampling administration of medical powder by means of an inhaler providing a compact arrangement without the need for instance for a space demanding spacer.
A continuous dry powder inhaler arrangement is disclosed, the arrangement being provided with electrostatically dosed medical powder onto an exchangeable dosing means like a cassette or the like for respiratory administration of medicaments into the deep or upper lung airways. The inhaler presents a compact integrated device with a case having a sliding lid, which can be placed in a closed position covering a mouthpiece or in an open position exposing this exchangeable mouthpiece. In the open lid position the device is ready to deliver a prepared pre-metered dose of medical powder upon-an inhalation via the exposed mouthpiece. Medical drugs are in advance dosed as medical powder and carried by an exchangeable dosing means and constitute dry powder substances or dry powder medical formulations prepared for continuous dosing. The exchangeable dosing member carries a number of sequentially accessible sealed doses. The sealing of the individual doses preserves a controlled storing, of powder during the total lifetime of a dosing cassette. This sealing is cut open during the inhalation process after that the device has been set into the open state by moving the sliding lid to the open position. The mouthpiece and/or the exchangeable dosing means of the device is preferably made out of dissipative and conductive materials to prevent electrostatic charge build-up during inhalation. Upon an inhalation the cassette carrying a selected dose is released into a longitudinal motion by a forcing spring, whereby the protective foil is cut open to let a nozzle of a suction tube access the powder. By a braking arrangement, the motion of the cassette is adjusted to such a speed that the time for the continuous delivery of the powder will be controlled and prolonged to an order of 0.5 to 5 seconds. The exchangeable dosing means normally presents a number of electrostatically deposited dry medical powder doses in the form of strips or a series of spots onto the dosing means. The DPI is adjusted for a systemic or a local lung setting with respect to activation pressure and closing pressure resulting in a 20 to 60 liter/minute inhalation air flow for systemic delivery setting and 40 to 80 liters/minute for a local lung setting. Furthermore the de-agglomeration power is adjusted between 0.1 and 6 watts to be used in the DPI by optimizing the pressure drop and inhalation flow rate by changes to the mouthpiece and/or the device member and their relation to each other. The DPI activation pressure is further adjusted to a value between 0.5 and 4 kPa and closing pressure between 0.5 and 4 kPa to eliminate the low power at the start and end of the inhalation. The inhaler arrangement further provides a number of special functions for a safe handling of the device, e.g. control of regular changes of mouthpiece and controls for a utilization of a pre-defined number of cassettes after which it must be discarded.